Here is an overview of NMS.

Learning objectives

-Recognize the tetrad of sx of NMS during patient care

-Diagnose NMS in practice

-Make recommendations to the team when suspecting NMS

Definition

• Neurologic emergency
• Syndrome associated with dopamine-blocking medications (especially antipsychotics)
  • Can also be from removal of dopaminergic med (carbidopa-levodopa)
• Classic tetrad (diagnostic criteria):
  • Mental status change
    • Confusion > psychosis, may progress to stupor/coma
    • Can see catatonia/mutism
  • Rigidity
    • Lead-pipe
  • Hyperthermia
    • Usually >38C, sometimes >40C
  • Autonomic instability
    • Tachycardia, labile/high BP, tachypnea, diaphoresis
• NOTE: Some cases don’t have all of these criteria. Consider NMS when ANY 2 of the tetrad occur in the setting of an antidopamine drug.

• Sx usually evolve over 1-3 days after:
  • High doses, rapid dose escalation, switching agents, parenteral administration
• Risk factors:
  • Lithium or other psychotropics, depot formulations, substance use, neurologic disease, acute medical illness, dehydration, infection, surgery

Typical Labs

• Leukocytosis (10-40K)
• Elevated LDH, ALP, LFT
• Electrolyte abnormalities
  • Hypocalcemia, hypomagnesemia, hypo/hypernatremia, hyperkalemia, metabolic acidosis
• Myoglobinuria from rhabdomyolysis
• Low serum iron common
• Elevated CK (1-10,000, can be much higher in severe cases)

Evaluation

• Diagnosis is confirmed by history (exposure to offending drug) and presence of supportive features. There is no single diagnostic test.
• Workup is to:
  • Exclude other causes
  • Detect complications
• There actually are DSM-TR criteria apparently but no single scoring system used in practice

DDx

• Serotonin syndrome
  • More hyperreflexia, clonus, GI symptoms
• Malignant hyperthermia
  • Anesthetic, succinylcholine exposure
• Malignant catatonia
• Intrathecal baclofen withdrawal
• Anticholinergic toxicity
• Stimulant intoxication
• Other serious conditions:
  • CNS infection
  • Sepsis
  • Seizures
  • Heat stroke

• Tetanus
• Alcohol withdrawal
• Thyrotoxicosis
• Pheochromocytoma
• Autoimmune encephalitis
• Acute porphyria

Management

• Stop offending drug immediately or restart dopaminergic drug
• Often requires ICU care
• Need to:
  • Maintain cardiorespiratory stability, give IV fluids, treat rhabdomyolysis-related kidney injury, control hyperthermia, control severe HTN, provide DVT prophylaxis
• Meds that can be used:
  • Lorazepam or other benzos
    • Lorazepam 1-2mg IM or IV q4-6h
    • Diazepam 10mg IV q8h
  • Dantrolene: 1-2.5 mg/kg IV, can repeat up to 10 mg/kg/day

• Bromocriptine: 2.5mg via NG tube q6-8h, titrate up to 40mg/day 
• Amantadine: 100mg PO or via gastric tube initially, titrate up to 200mg q12h
• ECT
  • Can be considered in refractory cases or when psychotropic tx is needed but can’t use antipsychotics
  • Limited evidence
  • Has safety risks, including cardiovascular complications

Possible complications

• Dehydration, electrolyte abnormalities, AKI, cardiac arrhythmias, MI, stress cardiomyopathy, respiratory failure, aspiration pneumonia, pulmonary embolism, VTE, sepsis

Prognosis

• Most cases resolve within 2 weeks, mean 4-11 days
• Longer illness in depot antipsychotics or structural brain disease
• Mortality: 5-10%, used to be higher
  • Death from systemic complications

Restarting antipsychotics

• There is a risk of recurrence, but unknown degree of risk
• Wait at least 2 weeks, use low-potency agents, start low/go slow, avoid lithium/dehydration
• Monitor carefully

Richa Vijayvargiya, MD

Psychiatry Service Director, UF Shands

Associate Program Director, UF Psychiatry Residency

Assistant Clinical Professor

UF Department of Psychiatry

Consultation-Liaison Division

rvijayvargiya@ufl.edu

Steroid-induced mental status changes are very common in the CL setting. Here is some teaching info to give you a general overview.

We can discuss this during teaching tomorrow:

Source: Open-Evidence

Steroid-Induced Mental Status Changes

Which steroids can cause mental status changes? At what doses?

-Any systemic glucocorticoid can cause neuropsychiatric effects

–Common culprits

• Prednisone / Prednisolone
• Methylprednisolone
• Dexamethasone
• Hydrocortisone

Steroids are often discussed in prednisone equivalents.

Dose relationship (prednisone equivalents)

• <20 mg/day → low risk
• 20–40 mg/day → moderate risk
• >40 mg/day → clearly increased risk
• >60–80 mg/day → high risk
• Pulse steroids (e.g., IV methylprednisolone 1 g/day) → very high risk

***Neuropsychiatric effects can occur even at low doses, particularly in vulnerable patients.

What mental status changes can steroids cause?

• Hypomania/mood elevation (most common)
• Mania (11%)
• Anxiety (8%)

• Insomnia
• Irritability / emotional lability
• Depression (more common in long-term use – 22%)

• Psychosis (delusions > hallucinations; ~5–10%)
• Delirium (16%)
• Cognitive impairment (attention, working memory)

What is the treatment? What is most effective?

Most effective treatment:
***Reduce or discontinue the steroid, if medically feasible.

If steroids cannot be stopped, treat symptomatically:

Anxiety / agitation / insomnia

• Low-dose antipsychotic (often very effective)
  • Quetiapine 12.5–50 mg
  • Olanzapine 2.5–5 mg
• Adjuncts
  • Trazodone
  • Melatonin
  • Gabapentin
• Benzodiazepines: short-term and cautious use only

Mania or psychosis

• Antipsychotic = first-line
  (olanzapine, risperidone, quetiapine)

Controlled trials support lithium and phenytoin for prevention of mood symptoms

***Antipsychotics are generally more effective than benzodiazepines.

How long do symptoms last after stopping steroids?

• Anxiety / insomnia: days
• Mania / psychosis: typically 1–2 weeks
• Occasionally up to 3–4 weeks
• Symptoms may persist longer after prolonged high-dose exposure

Improvement often begins within 48–72 hours of dose reduction.

How to distinguish steroid-induced anxiety from primary anxiety?

• Clear onset after steroid initiation or dose increase
• Prominent insomnia
• Restlessness / activation rather than worry-based rumination
• Often accompanied by:
  • Irritability
  • Mood elevation
  • Pressured thoughts

Who is at higher risk?

• High-dose steroid exposure
• Prior steroid-induced psychiatric reaction
• History of mood disorder (especially bipolar disorder)
• Older age
• Female  

• Hepatic or renal dysfunction
• Hypoalbuminemia
• ICU or severe medical illness
• Sleep deprivation

Richa Vijayvargiya, MD

Psychiatry Service Director, UF Shands

Associate Program Director, UF Psychiatry Residency

Assistant Clinical Professor

UF Department of Psychiatry

Consultation-Liaison Division

rvijayvargiya@ufl.edu